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Author
Topic: BLIP or low level viremia? (Read 13321 times)

Had what hoped was a viral load blip in February (100). Went back in for a retest in March and got a second count of 130. Full history in the sig line.

So need some advice on what usually comes next (Doc out of town this week). Is the protocol to test again or just assume some sort of low level resistance and move to a new set of drugs?

Never got a genotype either. So, if changing should I wait on the current meds until the viral load is high enough for a genotype? Or take a brief holiday to encourage enough virus to be able to test? (Seems a bit radical that -- think I might prefer to jump without a genotype instead, but maybe that is common?)

Currently on Kaletra / Truvada. I'm yearning to jump to a new combo anyway, given the lipid problems and the osteoporosis.

99%+ Over 2.75 years missed none of the Truvada and about 3 of the (half doses) of Kaletra. And quite good about the timing too (within 2 hours or so 99% or more of the time). For the past 6 months been 100%. So probably not the adherence thing. Middle age has its benefits after all

Adherence is really important, but not a guarantee, particularly if you start off with really high viral load and really low Tcell count.

But this may not even be resistance; levels aren't high enough to test. Starting with a lot of virus, there may be a lot in various reservoirs that are randomly released and occasionally blip up to detectable.

But do listen to your doctor, adherence is very important even if it is not everything.

Spoke to the doc. After consultation with various colleagues she doesn't see a need for monthly monitoring of the viral load since it is so low. If it rises above 500 we will do a genotype, but until then back to the 3 month comprehensive blood draws -- next one in May.

Not quite sure how I feel about this; one has a certain desire to do something rather than just wait. But the numbers are quite low...

As you know, many of us have or may a day or another experiment a blip.It doesn't means always virological failure, especially when the magnitude of the blip is low.

Take a look to the signature of some.For e.g. the one of J.R.EDiagnosed positive in 1985. In October of 2003, My t-cell count was 16. Percentage at that time was 5%. As of January 15, 09 t-cells are at 331. Viral load <50, since November of 04, except for two blips of 166 and 288. Current % is at 11% Next blood tests scheduled for April 14, 09

Now personally, if this should happen to me, I will made another blood draw after 1 month.Just to ensure that it is a blip. Most of labs can already identify resistances with a VL in the 500s despite above 1000 is better (as more mutations can be seen).

If you do a VL test in a month, you will know if it was a blip or not.If the VL has increased, then you can take a decision. If you become undetectectable, you can relax.

I wishes you that as for many it is just a blip.

NoteI am in the same shoes as you somehow. My VL is still undetectable, but I am always expecting to see a VL>40 due to my very first genotype (unsure if it is mine).And I will know by the end of this year I guess.A bit stressing no ? But we have no others choices to take it as it is and be patient and still enjoy our life.

I would definitely want to wait for it to go up and get the geno/pheno types done, but that's just me -- otherwise you're shooting in the dark. I'd probably get tested every 2 months instead of 3. 3 is what you do when everything is working.

Unfortunately I already did the test again one month later and still had a detectable viral load.

The first potential blip was in February with a viral load of 100. The second detectable result was in March (130).

Thus, the last lines of the study are what I'm looking at: "The study authors conclude by suggesting that blips “may not be cause for clinical concern,” and they call for further studies “to define when detectable viremia should trigger a change in therapy.” Until then, they postulate that “blips with a magnitude of greater than 200 copies/ml or blips that are detected in at least two independent or consecutive measurements may be more of a cause for concern.”

Since they are independent measurements they still could just be random fluctuation, but the likelihood of two consecutive blips if they are truly independent probabilities would be the square of the probability of just one, which is, of course, much smaller.

But it's hardly time to panic, even at a 30% compound growth rate in viral load per month there is plenty of time to get another test two months after the last one, which will get me back on schedule will my full 3 month battery. If that one is also detectable though it may be time to force the issue of a meds change upon my reluctant doc.

Actually it would be two months after the one month test which would get me back on schedule for a full set of three month labs -- just did viral load and nothing else at the one month test.

I am struggling with this question of waiting for it to go up to readable levels. I know there's studies suggesting low level viremia is not a good idea. If it has gone up to where I can get a geno/pheno at the next draw I guess I'll know what to do but if not...I guess I could take a brief holiday to let the virus multiply, do a draw and go back on while waiting for the results? But that seems like it might fail in a lot of different ways (wait too long and get sick, wait too little and not have anything measurable).

I'm not very good at just sitting on my hands ... but no doubt this is giving me the opportunity to develop the virtue of patience

The first one reminds me that I forgot to respond to your question on GFR. My labs have never indicated any abnormalities in GFR (unfortunately the labs don't show a number unless it is abnormal, so there is no way to do trend analysis).

Note that after consecutive detectable results most authors do not consider it a blip any more, so I'm more or less "defined out" of these papers' results . (e.g. "A detectable viral load measurement was considered a blip if there was one plasma HIV-RNA value between 50 to 1,000 copies/mL immediately preceded and followed by an undetectable measurement at less than 50 copies/mL. " ) If you see anything interesting on low level viremia though ...

Given where treatment was just a few short years ago, one side of me marvels at the fact that there are so many options these days to get one to and keep one at an undetectable status. I feel a bit guilty about it . . . but not so much that it is going to stop me from pursuing undetectable status.

It could still be a blip, although Newt makes a good point that there are better combos and changing meds might not be a bad thing anyway. Still, it would be nice to know for sure that you'd be changing because you wanted to and not due to resistance.

I spent years getting undetectable. The first time I did my combo included Fuzeon. I think it is very likely you would go undetectable and stay that way if you simply added Isentress. However, I agree with Newt, you might want to also consider swapping out the Kaletra for Reyataz or Prezista.

I think it is likely that adding an additional agent in another class will do the trick. Has your doctor even mentioned that to you?

But I think I know the answer, and its what Newt (Mr. Vermeer-Reyataz-glaze) said. I mainly have to figure out how to get the doc on board when I see her.

JJ -- we discussed intensification when I was taking over 18 months to get undetectable, but I was so close we did not act. I have a preference for change at this point given the other side effects, but ...

Long frustrating appointment with the ID doc yesterday; got quite forceful about the idea that there is more to treatment than just viral load and CD4 counts and that continuing lipids and osteoporosis matter too. End result is she will talk to her mentor on how to proceed -- looking potentially at Epzicom/Isentress.

In the meantime Dr. Gallant Web response suggests that if there were no baseline mutations, perhaps these results are just lab error and we should try an alternate test. Another reason to want to have had a genotype before starting ... live and learn.

One of the things you need to learn in dealing with doctors and your HIV treatment is that ultimately this is your decision and you body. From what your have mentioned about your doctor, she sounds difficult. It does matter about getting the virus knocked down. CD4's do matter. While lipids and osteo may be important, they are secondary concerns after getting a good regimen working for you.

You can always swap out the Kaletra and Truvada later if you want, but I would tell her I want to add Isentress. It is a very easy drug to take with almost no side effects. Then, later if you would like to swap out either the Kaletra or Truvada you can do so. However, Kaletra is a strong PI and Truvada I think easier in general than Epizicom. Epizicom has recently been getting attention for increased cardiovascular risk.

If you really want to go undetectable, add Isentress.

Plus, as those VL levels, you are unlikely to get a direction as far as resistance. You just have to do this one with your gut feeling. If your doctor does not see it your way, then find a new one!

In the meantime Dr. Gallant Web response suggests that if there were no baseline mutations, perhaps these results are just lab error and we should try an alternate test.

Is it possible to try that other viral load test Gallant mentioned (bDNA)? If you can have that done without it being a big deal (as far as coverage) then I think it's worth a try since it seems to offer more reliable numbers. If that one comes back below 75 or 50, then it's all been a blip but if it comes back higher then maybe there's some resistance.

So, following our last (rather tense) discussion my ID doc agreed to talk to her mentor who practices at a large city clinic and get back to me with ideas in a week.

Given the osteoporosis she is willing to swap out the Truvada, but prefers Epzicom to Combivir. She is sending a prescription for the genetic test for sensitivity to the Ziagen/abacavir component. If the test pans out she will switch Truvada out, starting as separate pills for Ziagen/abacavir and Epivir/lamivudine and then moving to Epzicom.

She is still noodling over what to replace Kaletra with -- I'm leaning quite hard for Isentress, but she likes a protease inhibitor. After discussing Prezista, (same amount of norvir as kaletra) and Reyataz (she doesn't like it with Ziagen) we wound back up at Isentress. I think we will land there.

On another track, met with the endocrinologist again about turning back the osteoporosis. I'm now fully back to normal from the weird fosamax reaction, and ready to try something else. This time it will be Actonel/risedronate. Like fosamax, it is usually given in a weekly (or even monthly) dose. But since it took 6 weeks for me to get back to normal after stopping the weekly fosamax, this time we will start the actonel as a daily dose and see how it goes -- that way if it also sends my blood pressure into orbit I can stop immediately and should get back to normal quickly.

Bought a new blood pressure monitor and will start the actonel in a week (had to special order a daily dose) with daily monitoring. I'll stage the drugs so that I'm sure there are no blood pressure problems from actonel before starting the Ziagen. (My blood pressure is usually fine -- but reacted badly to fosamax)

At any rate, high hopes that the viral load, lipids and osteoporosis will be on a better path by fall. Thanks for all the comments and suggestions.

After reading you latest post, I wonder why you would want to shortchange your next regimen with just Isentress and Epzicom. If I were having trouble getting undetectable I would add things not just change things and weaken them.

Epizicom is really just a swap for Truvada. Personally, I had weaker results with Epzicom than Truvada. I certainly don't think it is stronger than Truvada. You are just exchanging potential osteo for cardiac issues.

So, that leaves you with just Isentress. While it is certainly a stronger beast to get resistant to than a NNRTI, it is still much easier to become resistant to than a PI. If you become resistant to Isentress, you might throw away the best class for yourself in the future.

I stress again and invite comment - consider staying on a PI, swap the Truvada if you want to for Epzicom, add the Isentress. That will put less stress on the Isentress and certainly allow you to become undetectable faster.

Because, if you proceed with the Isentress/Epzicom option and it fails, you will likely require more agents anyway.

Well the test results are finally back and the genetic test for abacavir/Ziagen sensitivity ( HLA-B*5701) came back negative. So I'll be starting Ziagen/ Epivir / Isentress in about 3 weeks. I'll try them as separate drugs for a month and then move to Epzicom/Isentress.

I'm pretty happy, but a little nervous . . . Still am hoping for better long term side effects this time around.

Is it possible to try that other viral load test Gallant mentioned (bDNA)? If you can have that done without it being a big deal (as far as coverage) then I think it's worth a try since it seems to offer more reliable numbers. If that one comes back below 75 or 50, then it's all been a blip but if it comes back higher then maybe there's some resistance.

Inch, I tried the bDNA test this time and the viral load is still about the same I think (My copy of the labs hasn't arrived yet so I'm going from what the doc said over the phone -- she said it came in around 115 but there was some confusion/static at that point). But it was worth a try; thanks for the suggestion.

Epizicom is really just a swap for Truvada. Personally, I had weaker results with Epzicom than Truvada. I certainly don't think it is stronger than Truvada. You are just exchanging potential osteo for cardiac issues.

So, that leaves you with just Isentress. While it is certainly a stronger beast to get resistant to than a NNRTI, it is still much easier to become resistant to than a PI. If you become resistant to Isentress, you might throw away the best class for yourself in the future.

I stress again and invite comment - consider staying on a PI, swap the Truvada if you want to for Epzicom, add the Isentress. That will put less stress on the Isentress and certainly allow you to become undetectable faster.

Because, if you proceed with the Isentress/Epzicom option and it fails, you will likely require more agents anyway.

JJ thanks for your note; sorry I missed it before,

I guess I'm not sure that I'll need additional agents -- even given the similarity of Epivir and Emtriva it still looks to me like I'm swapping all three agents. It would be great to have a resistance test but I'm close enough to undetectable so that is not feasible. So I've been thinking it is a gamble and if it works I'm fine and if it doesn't I'll have enough virus to get a resistance test and formulate a better strategy. While I may lose Isentress as a possibility for the future, it does look like there are potential second line integrase inhibitors in the pipeline and several classes and a number of other drugs likely available.

My understanding is Epivir and Emtriva are almost identical - just mark those off the sheet. Substituting Ziagen for Viread is unlikely to give you any additional strength. Therefore, the weight of your new regimen will primarily fall on Isentress. I can assure you my doctor would never let me switch from Truvada/Kaletra to Isentress/Epzicom. Why? Because Kaletra is a strong medication.

At bare minimum, I would stay on the Kaletra with the Isentress for a couple of months until I went undetectable and then drop it. It gives you a good feeling to see that test come back <48.

Sorry but not quite following your arguments. Since I was undetectable for 9 months, but have since had persistent low level detectable status, my working hypothesis is that either1) there is more virus released from reservoirs than typical -- because of such a thorough infection and treatment delay, or2) Under pressure from current HAART have evolved a resistant strain that is only capable of weak replication.

If case 1 -- why would the new HAART mix be any worse than the old -- given that there is no replication going on (just release from reservoirs-- that implies no resistance has developed

If case 2 -- it would be great to know what the specific mutations are, but there is not enough virus to tell. But even so, viral replication rates are low and at least two of the drugs are entirely new including one from a new class entirely and the most common mutation in the third tends to enhance susceptability to other HAART. So why is the low barrier to resistance importantv-- that would appear to be the case when there is a high amount of viral replication.

To be honest i wouldn''t worry too much if your lab is using the latest viral load tests. They are so sensistive as to return more than 50 copies many times. It's worth finding out. My clinic, using the latest viral load tests, reports viral load of 100 or under as "undetectable".

I am withh jj on Isentress + PI + Truvada points

The (soon to be) new BHIVA guidelines on monitoring will recommend resistance tests regardless of viral load if this is above 50 copies. New tests are quite (surprisingly) sensitive.

Your point 1) on reservoirs is a non-sequitur since viral load measures peripheral blood viral load. If you want chapter and verse get a (painful, slightly dangerours spinal tap) CSF viral load test or (less painful, non-dangerous but not as informative) semen viral load test.

But most of all I wouldn't worry if your viral load is consistently around 100 or below. It might, even, pass/fall under 50 copies in due course.

If you're going the "Isentress + PI + Truvada" route I believe that several studies have shown a higher synergy in using (boosted) Prezista with Isentress, and indeed from my own personal experience with this combination I would agree.

Thanks guys -- was away camping without electronics for a couple of weeks so didn't respond -- but having thought about it some more I'll talk to the doctor about continuing the Kaletra as an intensifier to the new regimen until undetectable again.

My doc apparently forgot to call in the prescription so still have a while before starting.

Think I may have confused matters in this thread by having multiple issues that I'm trying to manage in addition to the low level viremia (viremia PLUS osteoporosis PLUS somewhat high lipids). Having thought about it, the viremia and the osteoporosis are the most important to me now, the lipids are only somewhat out of line so far and there are still more powerful statins to try. But I've already broken a wrist and the prospect of a wheelchair if I break something bigger is a real motivator to try to move backwards on the osteoporosis scale to osteopoenia or health -- so I do want to switch out the Truvada. (On a positive note, except for some joint pain, my second try at an osteoporosis drug is going well.)

The (soon to be) new BHIVA guidelines on monitoring will recommend resistance tests regardless of viral load if this is above 50 copies. New tests are quite (surprisingly) sensitive.

Newt Is there a special name for these new tests? My doc called up Labcorp (a major US lab) about a month ago to check on resistance testing options and they still said they needed a viral load of 500 or so to run the tests.

Got hold of the doc Friday -- looks like the drugs will be in and I'll start this coming Tuesday. She has started me with a one month supply of Isentress, Ziagen and Epivir and wants each drug started separately about 12 hours apart in case of any immediate and severe reactions. After a month we'll move to Epzicom/Isentress.

Talked to her about intensifying by keeping Kaletra until undetectable -- she was initially not warmed up to the idea, seemed to warm up more as a switch out of Truvada for Epzicom, intensifying with Isentress and eventually simplifying out the Kaletra -- but not persuaded yet, wants to discuss again Tuesday.

Well -- I've switched! Added Isentress two days ago, Ziagen yesterday and today dropped Truvada and added Epivir. Might have had a faint headache the first day but it went away in a half hour. Otherwise no tolerability problems yet.

Just got off the phone with the doctor and she is still unsure about keeping Kaletra but says she will monitor me for liver problems and see. She continues to have second thoughts about "using up" Isentress so fast -- she broached trying Sustiva/Epzicom. While I have some lingering desire to experience Sustiva (after all I never got to do mushrooms in my sedate youth ) since this combo seems tolerable, I'm a little hesitant to keep moving (and if I'm going to burn Isentress, wouldn't I have already done so?)

BTW she called Mayo and they also said they only had a 50% chance of doing a genotype with 500-1000 viral load.

Finally, I just yesterday got the paper copy of the lab report from July where I took the viral load using the branch DNA test. She also did the RNA PCR test and apparently got them mixed up when she called me. The PCR RNA viral load test is 130, the branch DNA test is ... undetectable! So, am thinking this was all much ado...

Oh well -- at least the tenofovir in Truvada is no longer eating away at my spine.

Finally, I just yesterday got the paper copy of the lab report from July where I took the viral load using the branch DNA test. She also did the RNA PCR test and apparently got them mixed up when she called me. The PCR RNA viral load test is 130, the branch DNA test is ... undetectable! So, am thinking this was all much ado...

Can't believe that I missed this thread...... I was having such a hard time getting to UD in the beginning - VL between 100ish and 600 for over a year. Finally did the bDNA test -- and bang, undetectable. Then I had to change labs, due to insurance -- which, of course, made me go elsewhere for my blood draws. I asked my doc to order one RNA test at the new site -- Undetectable! My (unproven) hypothesis -- the original site of my draw was simply not handling the sample properly. bDNA is far more forgiving of handling "issues". Believe me when I say, I am not one who jumps to the "lab error" explanation at the drop of a hat, but that is what I think was going on. I believe that I was UD from 3 months into treatment.Whenever I see threads like this I always strongly urge a bDNA test before changing a regimen. Sorry I missed yours!!

Inch, I tried the bDNA test this time and the viral load is still about the same I think (My copy of the labs hasn't arrived yet so I'm going from what the doc said over the phone -- she said it came in around 115 but there was some confusion/static at that point). But it was worth a try; thanks for the suggestion.

I don't get it? So your doctor knew the results of the bDNA was UD this whole time and was still discussing this with you as if you might have resistance?

If it's too convoluted to explain, I totally understand, there's no need to, it's just weird to me that based on what you said above your doctor at that point knew you were UD on the bDNA.

At any rate, it's good the Truvada is no longer eating away at your spine!

Can't believe that I missed this thread...... I was having such a hard time getting to UD in the beginning - VL between 100ish and 600 for over a year. Finally did the bDNA test -- and bang, undetectable. Then I had to change labs, due to insurance -- which, of course, made me go elsewhere for my blood draws. I asked my doc to order one RNA test at the new site -- Undetectable! My (unproven) hypothesis -- the original site of my draw was simply not handling the sample properly. bDNA is far more forgiving of handling "issues". Believe me when I say, I am not one who jumps to the "lab error" explanation at the drop of a hat, but that is what I think was going on. I believe that I was UD from 3 months into treatment.Whenever I see threads like this I always strongly urge a bDNA test before changing a regimen. Sorry I missed yours!!

Good luck,Mike

Thanks, but I don't think we need to invoke lab error to explain these particular results. I spent some time looking at studies of how bdna test results compare to PCR RNA results and it appears that there is a longstanding documented bias where PCR RNA viral load numbers tend to be higher than those reported by bDNA.

"...log10 values obtained by the US-RT-PCR assay were, on average, 1.05-fold higher than the log10 values obtained by the bDNA 3.0 assay (7). Similarly, the HIV-1 RNA levels obtained by the US-RT-PCR assay in our study were on average twofold higher than the levels obtained by the bDNA 3.0 assay for the same sample. "Journal of Clinical Microbiology, August 2000, p. 2837-2845, Vol. 38, No. 8Performance Characteristics of the QUANTIPLEX HIV-1 RNA 3.0 Assay for Detection and Quantitation of Human Immunodeficiency Virus Type 1 RNA in Plasma Alejo Erice,1,,* Donald Brambilla,2,3 James Bremer,3,4 J. Brooks Jackson,5, Robert Kokka,6 Belinda Yen-Lieberman,7 and Robert W. Coombs8,

So a PCR RNA viral load of 130 appears consistent with a bdna viral load of under 75.

This is further supported by the fact that it has been the same lab all along and I was undetectable for 9 monthsbefore becoming detectable again and I've since had 4 detectable results of 100 to 150. I go at the same time of day etc. ... Finally since its the lab my doc sent me to in the first place it would appear likely that I would not be the only person my doctor sees who would have this issue.

Glad to hear it is working for you. Personally, after a few good labs I might swap out the Kaletra for something a little more lipid friendly like Prezista or Reyataz. Since you are undetectable now, you might even consider an NNRTI. I skipped using Sustiva and now take Intelence.

Noticed that the new US treatment guidelines explicitly address this issue and raises many of the questions and opinions that came up here. But they don't have a firm answer either. Still, since low level viremia is relatively rare and people sometimes search the forums for relatively rare occurrences, thought I'd update the thread to reflect the new guidelines.

Here's what they say under how to handle treatment failure for different scenarios

Prior treatment with low-level viremia (50–1,000 copies/mL). Assess adherence. Consider variability in HIV RNA assays. Patients with isolated increases in HIV RNA (“blips”) do not require a change in treatment [13] (AII). Some HIV RNA assays are associated with more frequent “blips” [31] and results should be interpreted with caution. It is not clear how to manage patients with persistent low-level viremia; many experts would not change therapy and would follow the patient closely (CII). http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf p.68

While my doctor was in line with the experts who "would not change therapy", because of the long term side effects (cholesterol and bone mineral density) I persuaded her to change regimens. We temporarily intensified (to 4 drugs rather than 3) until getting back to undetectable and then moved wholly to the new regimen.